dbSNP rs2273797: LMO2:c.464+68G>A (chr11-33864534-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005574.4(LMO2):c.464+68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,329,298 control chromosomes in the GnomAD database, including 24,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3307 hom., cov: 32)

Exomes 𝑓: 0.19 ( 21492 hom. )

Consequence

LMO2
NM_005574.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.592

Publications

5 publications found

Variant links:

Genes affected

LMO2 (HGNC:6642): (LIM domain only 2) LMO2 encodes a cysteine-rich, two LIM-domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number T-cell acute lymphoblastic leukemia-specific translocations occur. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Nov 2008]

LMO2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005574.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LMO2	NM_005574.4	MANE Select	c.464+68G>A	intron	N/A	NP_005565.2	P25791-3
LMO2	NM_001142315.2		c.257+68G>A	intron	N/A	NP_001135787.1	P25791-1
LMO2	NM_001142316.2		c.257+68G>A	intron	N/A	NP_001135788.1	P25791-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LMO2	ENST00000257818.3	TSL:1 MANE Select	c.464+68G>A	intron	N/A	ENSP00000257818.2	P25791-3
LMO2	ENST00000395833.7	TSL:1	c.257+68G>A	intron	N/A	ENSP00000379175.3	P25791-1
LMO2	ENST00000411482.1	TSL:1	n.*201+68G>A	intron	N/A	ENSP00000401967.1	P25791-4

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31049

AN:

151906

Hom.:

3300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.186

AC:

219215

AN:

1177274

Hom.:

21492

AF XY:

0.189

AC XY:

111228

AN XY:

587092

show subpopulations

African (AFR)

AF:

0.245

AC:

6923

AN:

28238

American (AMR)

AF:

0.126

AC:

4735

AN:

37630

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

4655

AN:

21388

East Asian (EAS)

AF:

0.273

AC:

9929

AN:

36432

South Asian (SAS)

AF:

0.268

AC:

19247

AN:

71810

European-Finnish (FIN)

AF:

0.205

AC:

8401

AN:

41042

Middle Eastern (MID)

AF:

0.281

AC:

999

AN:

3558

European-Non Finnish (NFE)

AF:

0.174

AC:

154541

AN:

886562

Other (OTH)

AF:

0.193

AC:

9785

AN:

50614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

9129

18258

27386

36515

45644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5280

10560

15840

21120

26400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.204

AC:

31079

AN:

152024

Hom.:

3307

Cov.:

AF XY:

0.209

AC XY:

15541

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.244

AC:

10108

AN:

41448

American (AMR)

AF:

0.169

AC:

2587

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

762

AN:

3472

East Asian (EAS)

AF:

0.274

AC:

1413

AN:

5148

South Asian (SAS)

AF:

0.281

AC:

1347

AN:

4802

European-Finnish (FIN)

AF:

0.210

AC:

2227

AN:

10588

Middle Eastern (MID)

AF:

0.308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.175

AC:

11888

AN:

67960

Other (OTH)

AF:

0.204

AC:

432

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1249

2498

3746

4995

6244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

4501

Bravo

AF:

0.203

Asia WGS

AF:

0.255

AC:

887

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.13

(source)

DANN

Benign

0.68

PhyloP100

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over